RUI: Frequency-Dependent Modulation of Hippocampal Neural Circuit in Freely Moving Rats

这项研究将有助于清楚地了解局部神经回路如何对各种输入做出反应，从而决定信息在大脑中的整体处理方式。海马结构是一种与学习和记忆过程密切相关的大脑结构，该研究涉及海马结构，拟议的研究旨在量化海马结构内特定神经元电路在受到不同输入(即具有不同突发频率的破伤化范例)时的调制。研究人员的假设是，齿状细胞反应的调制依赖于激活这一神经元回路的破伤化范例的“突发频率”。这一点很重要，因为穿支通路中的放电模式由每25ms发生一次的4-6个动作电位组成，从而向海马结构的齿状颗粒细胞发送一种爆发性的激活模式。研究表明，内侧穿支通路(海马结构的主要输入通路之一)的Tetan化可以在齿状颗粒细胞层诱导长时程增强(LTP)。这种神经回路是海马三突触回路的第一支，这种调制影响了神经元传入和通过海马结构的门控；因此，它可能在早期生活和整个成年期的学习和记忆发展中发挥重要作用。这项研究是生物医学工程和神经生物学领域的独特合作伙伴关系，融合了这两个学科的方法和技术，以提供关于神经电路性能的重要见解，这些神经电路能够在成熟时修改它们的反应。从即将进行的实验中获得的结果预计将产生比直接研究更多的好处。首先，将要开发的用于记录自由活动的断奶前动物的生物电数据的微型刺激和记录方法可以被其他人用于广泛的应用。其次，所获得的数据可以用来在未来延伸这一研究路线。

0451285BronzinoThis investigation will contribute to developing a clear understanding of how local neural circuits respond to various inputs in determining how information is processed globally in the brain. The hippocampal formation, a brain structure intimately involved in learning and memory processes, is involved and the proposed studies are designed to quantify the modulation of a specific neuronal circuit within the hippocampal formation when it is subjected to different inputs (i.e., tetanization paradigms with varying burst frequencies). The investigators hypothesis is that modulation of the dentate cellular response is dependent upon the "burst frequency" of the tetanization paradigm activating this neuronal circuit. This is important as the pattern of firing in the perforant path consists of trains of 4-6 action potentials occurring every 25 ms, thereby sending a bursting pattern of activation to the dentate granule cells of the hippocampal formation. Tetanization of the medial perforant path (one of the major input pathways to the hippocampal formation) has been shown to induce long-term potentiation (LTP) in the dentate granule cell layer. This neural circuit serves as the first leg in the hippocampal trisynaptic circuit and such modulation influences the gating of neuronal transmission into and through the hippocampal formation; it therefore may play an important role in the development of learning and memory both in early life and throughout adulthood. The investigation is a unique partnership of the fields of biomedical engineering and neurobiology, melding the approaches and techniques of both disciplines to provide important insights regarding the performance of neural circuits capable of modifying their responses as they mature. Results obtained from the experiments to be conducted are expected to have benefits beyond the immediate studies. First, the miniaturized stimulation and recording methodologies that are to be developed to record bioelectric data in the freely moving pre-weaning animal can be used by others in a wide variety of applications. Second, the data acquired can be utilized to extend this line of research in the future.